Experience With Elexacaftor/Tezacaftor/Ivacaftor in Patients With Cystic Fibrosis and Advanced Disease.

INTRODUCTION: Elexacaftor/tezacaftor/ivacaftor (ETI) was used through the early access programme in Spain from December 2019 in cystic fibrosis (CF) patients with homozygous or heterozygous F508del mutation with advanced lung disease. METHODOLOGY: Multicentre, ambispective, observational, study in which 114 patients in follow-up in 16 national CF units were recruited. Clinical data, functional tests, nutritional parameters, quality of life questionnaires, microbiological isolates, number of exacerbations, antibiotic treatments and side effects were collected. The study also compared patients with homozygous and heterozygous F508del mutations. RESULTS: Of the 114 patients, 85 (74.6%) were heterozygous for F508del mutation, and the mean age was 32.2±9.96 years. After 30 months of treatment, lung function measured by FEV1% showed improvement from 37.5 to 48.6 (p<0.001), BMI increased from 20.5 to 22.3 (p<0.001), and all isolated microorganisms decreased significantly. The total number of exacerbations was also significantly reduced from 3.9 (±2.9) to 0.9 (±1.1) (p<0.001). All items in the CFQ-R questionnaire showed improvement, except for the digestive domain. Oxygen therapy use decreased by 40%, and only 20% of patients referred for lung transplantation remained on the active transplant list. ETI was well-tolerated, with only 4 patients discontinuing treatment due to hypertransaminemia. CONCLUSIONS: ETI decreases the number of exacerbations, increases lung function and nutritional parameters, decrease in all isolated microorganisms, for 30 months of treatment. There is an improvement in the CFQ-R questionnaire score except for the digestive item. It is a safe and well-tolerated drug.

A Pilot Study on the Prediction of Non-Contact Muscle Injuries Based on ACTN3 R577X and ACE I/D Polymorphisms in Professional Soccer Athletes.

Muscle injuries are among the main reasons for medical leavings of soccer athletes, being a major concern within professional teams and their prevention associated with sport success. Several factors are associated with a greater predisposition to injury, and genetic background is increasingly being investigated. The aim of this study was to analyze whether ACTN3 R577X and ACE I/D polymorphisms are predictors of the incidence and severity of muscle injury in professional soccer athletes from Brazil, individually and in association. Eighty-three professional athletes from the first and second divisions of the Brazilian Championship were evaluated regarding the polymorphisms through blood samples. Nighty-nine muscle injuries were identified during the seasons of 2018, 2019 and 2020 and categorized according to severity. ACTN3 XX individuals had a higher frequency of severe injuries compared to the RX and RR genotypes (p = 0.001), and in the dominant model (compared to RX+RR), with p < 0.001. The trend p-value test showed an increased number of injuries/season following the order XX > RX > RR (p = 0.045). Those with the ACE II genotype had almost 2 fold the number of injuries per season compared to those with the ID+DD genotypes (p = 0.03). Logistic regression showed that the polymorphisms are predictors of the development of severe injury (ACTN3 R577X model with p = 0.004, R2: 0.259; ACE I/D model with p = 0.045, R2: 0.163), where ACTN3 XX individuals were more likely to suffer from severe injury (OR: 5.141, 95% CI: 1.472-17.961, p = 0.010). The combination of the ACTN3 577X allele and the ACE II genotype showed an increased number of injuries per season, enhanced by 100% (1.682 injuries/season versus 0.868 injuries/season, p = 0.016). Our findings suggest that both polymorphisms ACTN3 R577X and ACE I/D (and their interaction) are associated with the susceptibility and severity of non-contact muscle injury in soccer players.

Trajectories of Severe Exacerbations of Chronic Obstructive Pulmonary Disease and Their Relationship with Mortality Risk.

PURPOSE: Acute exacerbations of COPD (AECOPD) are important factors contributing to mortality risk. The rate of exacerbations varies overtime. An inconsistent pattern of exacerbation occurrence is a common finding. The mortality risk associated with such a pattern is not entirely clear. Our objective was to assess the risk of mortality associated with various possible patterns of AECOPD trajectories. METHODS: This is a multicenter historical cohort study. Four different exacerbation trajectories were defined according to the incidence of severe AECOPD requiring hospital admission 2 years before and after the date of the first visit to the respiratory clinic-Consistent non-exacerbators (NEx): no AECOPD before or after the index date; consistent exacerbators (Ex): at least one AECOPD both before and after the index date; converters to exacerbators (CONV-Ex): no exacerbations before and at least one AECOPD after the index date; converters to non-exacerbators (CONV-NEx): at least one AECOPD before the index date, and no exacerbations after said date. All-cause mortality risk for these trajectories was assessed. RESULTS: A total of 1713 subjects were included in the study: NEx: 1219 (71.2%), CONV-NEx: 225 (13.1%), CONV-Ex: 148 (8.6%), Ex: 121 (7.1%). After correcting for confounding variables, the group with the highest mortality risk was Ex. The CONV-Ex and CONV-Nex groups had a mortality risk between Ex and NEx, with no significant differences between them. CONCLUSION: Different possible trajectories of severe AECOPD before and after a first specialized consultation are associated with different mortality risks. An inconsistent pattern of exacerbations has a mortality risk between Ex and NEx, with no clear differences between CONV-Ex and CONV-NEx.

Evaluation of the multimorbidity network and its relationship with clinical phenotypes in chronic obstructive pulmonary disease: The GALAXIA study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous condition, in which taking into consideration clinical phenotypes and multimorbidity is relevant to disease management. Network analysis, a procedure designed to study complex systems, allows to represent connections between the distinct features found in COPD. METHODS: Network analysis was applied to a cohort of patients with COPD in order to explore the degree of connectivity between different diseases, taking into account the presence of two phenotypic traits commonly used to categorize patients in clinical practice: chronic bronchitis (CB+ /CB- ) and the history of previous severe exacerbations (Ex+ /Ex- ). The strength of association between diseases was quantified using the correlation coefficient Phi (ɸ). RESULTS: A total of 1726 patients were included, and 91 possible links between 14 diseases were established. Although the four phenotypically defined groups presented a similar underlying comorbidity pattern, with special relevance for cardiovascular diseases and/or risk factors, classifying patients according to the presence or absence of CB implied differences between groups in network density (mean ɸ: 0.098 in the CB- group and 0.050 in the CB+ group). In contrast, between-group differences in network density were small and of questionable significance when classifying patients according to prior exacerbation history (mean ɸ: 0.082 among Ex- subjects and 0.072 in the Ex+ group). The degree of connectivity of any given disease with the rest of the network also varied depending on the selected phenotypic trait. The classification of patients according to the CB- /CB+ groups revealed significant differences between groups in the degree of conectivity between comorbidities. On the other side, grouping the patients according to the Ex- /Ex+ trait did not disclose differences in connectivity between network nodes (diseases). CONCLUSIONS: The multimorbidity network of a patient with COPD differs according to the underlying clinical characteristics, suggesting that the connections linking comorbidities between them vary for different phenotypes and that the clinical heterogeneity of COPD could influence the expression of latent multimorbidity. Network analysis has the potential to delve into the interactions between COPD clinical traits and comorbidities and is a promising tool to investigate possible specific biological pathways that modulate multimorbidity patterns.

Gene Expression of ABHD6, a Key Factor in the Endocannabinoid System, Can Be Modulated by Female Hormones in Human Immune Cells.

One of the main risk factors for the development of an autoimmune disease is to be a woman. Much attention has been given to the involvement of female hormones in their etiology and sexual bias, although the mechanisms behind this potentially strong contribution in disease susceptibility are poorly understood. ABHD6 gene was recently identified as a risk factor for system lupus erythematosus and the risk was correlated with overexpression of the gene. ABHD6 is an enzyme that degrades the 2-arachidonoylglycerol, an endocannabinoid with immunomodulatory effects. Thus its degradation could contribute to immune dysregulation and development of autoimmune reactions. Sex hormones, such as estrogens, are believed to regulate important genes in the endocannabinoid pathway. However, no study was available regarding the effect of these hormones in human immune cells. In this study, ABHD6 expression was evaluated by quantitative PCR in leukocytes from healthy male and females and in the presence of estrogen or progesterone (PG). A statistical increase in ABHD6 expression could be detected in women. In the presence of estrogen or PG, a statistical upregulation of ABHD6 was observed, and in a sex-dependent manner, as only female cells responded to stimulation. Our results suggest that female hormones can promote the overexpression of ABHD6 in immune cells. This can potentially contribute to a pro-inflammatory scenario and partially explain the association of this gene in the development of LES, a highly female-biased disease.

DNA barcoding reveals the mislabeling of fish in a popular tourist destination in Brazil.

The consumption of raw fish has increased considerably in the West, since it is said to be potentially healthier than processed fish (for containing omega 3 and 6, essential amino acids and vitamins). However this potential benefit, as well as the taste, value and even the risk of extinction are not the same for all species of fish, constituting grounds for fraud. Using the principles of the DNA barcode we revealed mislabelling of fish in Japanese restaurants and fishmarkets in Florianópolis, a popular tourist capital in Brazil. We sequenced the COI gene of 65 samples from fisheries and 80 from restaurants and diagnosed 30% of mislabeled samples in fisheries and 26% in restaurants. We discussed that frauds may have occurred for different reasons: to circumvent surveillance on threatened species; to sell fish with sizes smaller than allowed or abundant species as being a much rarer species (law of supply); to induce product consumption using species with better taste. It should be noted that some substitutions are derived from incorrect identification and are not a fraud per se; they are due to confusion of popular names or misunderstanding by the sellers. Therefore, we suggest the implementation of a systematic regulatory program conducted by governmental agencies to reduce mislabelling in order to avoid further damage to the community (in health and financial issues) and fish stocks.

Origin and dynamics of admixture in Brazilians and its effect on the pattern of deleterious mutations.

While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6-8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes.

Population genetic analysis of insertion-deletion polymorphisms in a Brazilian population using the Investigator DIPplex kit.

The aim of this study was to estimate the diversity of 30 insertion/deletion (INDEL) markers (Investigator(®) DIPplex kit) in a sample of 519 individuals from six Brazilian states and to evaluate their applicability in forensic genetics. All INDEL markers were found to be highly polymorphic in the Brazilian population and were in Hardy-Weinberg equilibrium. To determine their forensic suitability in the Brazilian population, the markers were evaluated for discrimination power, match probability and exclusion power. The combined discrimination power (CDP), combined match power (CMP) and combined power of exclusion (CPE) were higher than 0.999999, 3.4 × 10(-13) and 0.9973, respectively. Further comparison of 29 worldwide populations revealed significant genetic differences between continental populations and a closer relationship between the Brazilian and European populations.

Population genetic data and forensic parameters of 30 autosomal InDel markers in Santa Catarina State population, Southern Brazil.

The application of DNA technology in forensic investigations has grown rapidly in the last 25 years and with an exponential increase of short tandem repeats (STRs) data, usually presented as allele frequencies, that may be later used as databases for forensic and population genetics purposes. Thereby, classes of molecular markers such as single nucleotide polymorphisms and insertions/deletions (InDels) have been presented as another option of genetic marker sets. These markers can be used in paternity cases, when mutations in STR polymorphisms are present, as well as in highly degraded DNA analysis. In the present study, the allele frequencies and heterozygosity (H) of a 30 InDel markers set were determined and the forensic efficacy was evaluated through estimation of discrimination power (DP), match probability, typical paternity index and power of paternity exclusion in 108 unrelated volunteers from the State of Santa Catarina (South Brazil). The observed H per locus showed a range between 0.370 and 0.574 (mean = 0.479). HLD128 was the locus with the highest DP (DP = 0.656). DP for all markers combined was greater than 99.9999999999646 % which provides satisfactory levels of information for forensic demands. Genetic comparisons (exact tests of population differentiation and pairwise genetic distances) revealed that the population of Santa Catarina State differs from Korea and USA Afro-American populations but is similar to the Portuguese, German, Polish, Spanish and Basque populations.

Lack of association between interleukin-18 polymorphisms and rheumatoid arthritis.

OBJECTIVE: To assess the association of the polymorphisms of the interleukin-18 (IL-18) gene with rheumatoid arthritis (RA) and with risk factors for cardiovascular diseases (CVD). METHODS: This sample comprised 97 patients with RA and 151 healthy controls. In the patients, risk factors for CVD were analyzed, such as cholesterol levels, arterial hypertension, smoking habit, C-reactive protein (CRP) level, and rheumatoid factor. DNA was extracted and the single nucleotide polymorphisms (SNP) at the -607C/A and -137G/C positions of the IL-18 gene were assessed in both groups. The Hardy-Weinberg equilibrium (HWE) was calculated and the odds ratio (OR) test performed, considering a 95% CI and P < 0.05. RESULTS: The frequencies of the -607A allele in patients with RA and in controls were 0,443 and 0.424, respectively, and of the -137C allele, 0.304 and 0.291, respectively. The genotype frequencies were in HWE, except for controls in the -137 locus (P = 0.006). Association of the polymorphisms of the IL-18 gene was found with neither RA nor risk factors for CVD, including cholesterol level and CRP (P > 0.05). In addition, more smokers were found among patients with RA as compared with controls (OR = 1.691; P = 0.088), and the CRP levels were slightly higher in patients who smoked than in patients who did not (OR = 2.673; P = 0.061). CONCLUSIONS: In this sample of patients with RA in the South of Brazil, association of the polymorphisms of the IL-18 gene was observed with neither RA nor risk factors for CVD.

Ausência de associação entre os polimorfismos do gene interleucina-18 e artrite reumatoide / Lack of association between interleukin-18 polymorphisms and rheumatoid arthritis

OBJETIVO: Analisar a associação dos polimorfismos do gene interleucina-18 (IL-18) com artrite reumatoide (AR) e com fatores de risco de doenças cardiovasculares (DCV). MÉTODOS: A amostra foi constituída por 97 pacientes com AR e 151 controles saudáveis. Nos primeiros, foram analisados fatores de risco de DCV, tais como níveis do colesterol, hipertensão arterial, tabagismo e fator reumatoide, bem como o nível da proteína C-reativa (CRP). O DNA foi extraído e foram analisados os polimorfismos de nucleotídeo único (SNP) nas posições -607C/A e -137G/C do gene IL-18 em ambos os grupos. O equilíbrio de Hardy-Weinberg (EHW) e o odds ratio (OR) foram realizados, considerando IC 95% e P < 0,05. RESULTADOS: As frequências do alelo -607A nos pacientes com AR e nos controles foram de 0,443 e 0,424 e do alelo -137C foram de 0,304 e 0,291, respectivamente. As frequências do genótipo estavam em EHW, exceto em controles no locus -137 (P = 0,006). Não foi encontrada associação dos polimorfismos do gene IL-18 com AR, nem com fatores de risco de DCV, incluindo o nível do colesterol e de CRP (P > 0,05). Além disso, observaram-se mais indivíduos fumantes entre pacientes com AR em comparação aos controles (OR = 1,691; P = 0,088), e os níveis de CRP eram ligeiramente mais elevados em pacientes fumantes quando comparados aos de pacientes não fumantes (OR = 2,673; P = 0,061). CONCLUSÕES: Ao analisar uma amostra de pacientes com AR no sul do Brasil, não foi encontrada associação dos polimorfismos do gene IL-18 com AR, nem com os fatores de risco de DCV.

OBJECTIVE: To assess the association of the polymorphisms of the interleukin-18 (IL-18) gene with rheumatoid arthritis (RA) and with risk factors for cardiovascular diseases (CVD). METHODS: This sample comprised 97 patients with RA and 151 healthy controls. In the patients, risk factors for CVD were analyzed, such as cholesterol levels, arterial hypertension, smoking habit, C-reactive protein (CRP) level, and rheumatoid factor. DNA was extracted and the single nucleotide polymorphisms (SNP) at the -607C/A and -137G/C positions of the IL-18 gene were assessed in both groups. The Hardy-Weinberg equilibrium (HWE) was calculated and the odds ratio (OR) test performed, considering a 95% CI and P < 0.05. RESULTS: The frequencies of the -607A allele in patients with RA and in controls were 0,443 and 0.424, respectively, and of the -137C allele, 0.304 and 0.291, respectively. The genotype frequencies were in HWE, except for controls in the -137 locus (P = 0.006). Association of the polymorphisms of the IL-18 gene was found with neither RA nor risk factors for CVD, including cholesterol level and CRP (P > 0.05). In addition, more smokers were found among patients with RA as compared with controls (OR = 1.691; P = 0.088), and the CRP levels were slightly higher in patients who smoked than in patients who did not (OR = 2.673; P = 0.061). CONCLUSIONS: In this sample of patients with RA in the South of Brazil, association of the polymorphisms of the IL-18 gene was observed with neither RA nor risk factors for CVD.

X-chromosomal genetic diversity and linkage disequilibrium patterns in Amerindians and non-Amerindian populations.

OBJECTIVES: We report X-chromosomal linkage disequilibrium (LD) patterns in Amerindian (Kogi, Wayuu, and Zenu) and admixed Latin American (Central Valley of Costa Rica and Southern Brazilian Gaucho) populations. METHODS: Short tandem repeats (STRs) widespread along the X-chromosome were investigated in 132 and 124 chromosomes sampled from the Amerindian tribes and the admixed Latin American populations, respectively. Diversity indexes (gene diversity and average numbers of alleles per locus) were estimated for each population and the level of LD was inferred with an exact test. RESULTS: The Amerindian populations presented lower genetic diversity and a higher proportion of loci in LD than the admixed ones. Two haplotype blocks were identified in the X-chromosome, both restricted to the Amerindians. The first involved DXS8051 and DXS7108 in Xp22.22 and Xp22.3, while the second found only among the Kogi, included eight loci in a region between Xp11.4 and Xq21.1. CONCLUSIONS: In accordance to previous work done with other populations, human isolates, such as Amerindian tribes, seem to be an optimal choice for the implementation of association studies due to the wide extent of LD which can be found in their gene pool. On the other hand, the low proportion of loci in LD found in both admixed populations studied here could be explained by events related to their history and similarities between the allele frequencies in the parental stocks.

Genetic signatures of parental contribution in black and white populations in Brazil.

Two hundred and three individuals classified as white were tested for 11 single nucleotide polymorphisms plus two insertion/deletions in their Y-chromosomes. A subset of these individuals (n = 172) was also screened for sequences in the first hypervariable segment of their mitochondrial DNA (mtDNA). In addition, complementary studies were done for 11 of the 13 markers indicated above in 54 of 107 black subjects previously investigated in this southern Brazilian population. The prevalence of Y-chromosome haplogroups among whites was similar to that found in the Azores (Portugal) or Spain, but not to that of other European countries. About half of the European or African mtDNA haplogroups of these individuals were related to their places of origin, but not their Amerindian counterparts. Persons classified in these two categories of skin color and related morphological traits showed distinct genomic ancestries through the country. These findings emphasize the need to consider in Brazil, despite some general trends, a notable heterogeneity in the pattern of admixture dynamics within and between populations/groups.

Genetic signatures of parental contribution in black and white populations in Brazil

Two hundred and three individuals classified as white were tested for 11 single nucleotide polymorphisms plus two insertion/deletions in their Y-chromosomes. A subset of these individuals (n = 172) was also screened for sequences in the first hypervariable segment of their mitochondrial DNA (mtDNA). In addition, complementary studies were done for 11 of the 13 markers indicated above in 54 of 107 black subjects previously investigated in this southern Brazilian population. The prevalence of Y-chromosome haplogroups among whites was similar to that found in the Azores (Portugal) or Spain, but not to that of other European countries. About half of the European or African mtDNA haplogroups of these individuals were related to their places of origin, but not their Amerindian counterparts. Persons classified in these two categories of skin color and related morphological traits showed distinct genomic ancestries through the country. These findings emphasize the need to consider in Brazil, despite some general trends, a notable heterogeneity in the pattern of admixture dynamics within and between populations/groups.

Pre- and post-Columbian gene and cultural continuity: the case of the Gaucho from southern Brazil.

OBJECTIVE: To investigate the evolutionary and demographic history of the Gaucho, a distinct population of southern Brazil, relating it to their culture, to assess possible parallel continuity. METHODS: Six binary polymorphisms, an Alu insertion polymorphism (YAP) and 12 short tandem repeat loci in the non-recombining region of the Y-chromosome, as well as the sequence of the first hypervariable segment (HVS-I) of the mitochondrial DNA (mtDNA) control region were studied in 150 unrelated males born in the Pampa region of Rio Grande do Sul. RESULTS: Comparison of the results with the other Brazilian and Uruguayan populations, as well as with their putative ancestors, indicated a stronger male Spanish influence than that observed elsewhere in Brazil, a former Portuguese colony. Extensive mtDNA analyses of their Amerindian component gave clear indications of the presence there of material from extinct (Charrua), as well as extant (Guarani) tribes. CONCLUSIONS: The genetic analyses contributed in a significant way to reveal that the known cultural continuity between pre- and post-Columbian Pampa populations was also accompanied by an extraordinary genetic continuity.

Niger-Congo speaking populations and the formation of the Brazilian gene pool: mtDNA and Y-chromosome data.

We analyzed sequence variation in the mitochondrial DNA (mtDNA) hypervariable segment I (HVS-I) from 201 Black individuals from two Brazilian cities (Rio de Janeiro and Porto Alegre), and compared these data with published information from 21 African populations. A subset of 187 males of the sample was also characterized for 30 Y-chromosome biallelic polymorphisms, and the data were compared with those from 48 African populations. The mtDNA data indicated that respectively 69% and 82% of the matrilineages found in Rio de Janeiro and Porto Alegre originated from West-Central/Southeast Africa. These estimates are in close agreement with historical records which indicated that most of the Brazilian slaves who arrived in Rio de Janeiro were from West-Central Africa. In contrast to mtDNA, Y-chromosome haplogroup analysis did not allow discrimination between places of origin in West or West-Central Africa. Thus, when comparing these two major African regions, there seems to be higher genetic structure with mtDNA than with Y-chromosome data.

Demographic and evolutionary trajectories of the Guarani and Kaingang natives of Brazil.

A total of 278 individuals from two Brazilian Indian tribes (Guarani and Kaingang) living in five different localities had their mitochondrial DNA sequenced for the first hypervariable segment (HVS-I), and a fraction of them was also studied for seven biallelic Y-chromosome polymorphisms. Nineteen HVS-I lineages were detected, which showed distinct distributions in the two tribes. The G(ST) value obtained with the mtDNA data is about 5 times higher for the Guarani as compared to the Kaingang, suggesting a higher level of differentiation between the three Guarani partialities than between the two Kaingang villages. Non-Amerindian admixture varied with sex and in the Guarani was only observed through the paternal line. Using these data and those of other Tupian and Jêan tribes, it was possible to make inferences about past migratory movements and the genetic differentiation of these populations.

MtDNA haplogroup analysis of black Brazilian and sub-Saharan populations: implications for the Atlantic slave trade.

Seventy individuals from two African and four black Brazilian populations were studied for the first hypervariable segment of mtDNA. To delineate a more complete phylogeographic scenario of the African mtDNA haplogroups in Brazil and to provide additional information on the nature of the Atlantic slave trade, we analyzed our data together with previously published data. The results indicate different sources of African slaves for the four major Brazilian regions. In addition, the data revealed patterns that differ from those expected on the basis of historical registers, thus suggesting the role of ethnic sex differences in the slave trade.

Heterogeneity of the genome ancestry of individuals classified as White in the state of Rio Grande do Sul, Brazil.

One hundred nineteen individuals classified as White, living in different localities of the Brazilian state of Rio Grande do Sul, were studied in relation to the HVS-I region of the mitochondrial DNA (mtDNA). The male fraction of the sample (N = 74) was also tested for seven Y-chromosome polymorphisms. In a specific population (Veranópolis), a city characterized by a large influence of the Italian immigration of the 19th century, the results from the maternal and paternal sides indicated almost complete European ancestry. However, another sample identified as White, from different localities of Rio Grande do Sul, presented significant fractions of Native American (36%) and African (16%) mtDNA haplogroups. These results indicate that Brazilian populations are remarkably heterogeneous; while some present an overwhelming majority of transplanted European genomes, with a complete correspondence between physical appearance and ancestry, others reflect a history of extensive admixture with dissociation between physical appearance and ancestry.